Based on observations that acute infusions of prostaglandins are natriuretic and that prostaglandins inhibit tubular transport of sodium and chloride, the hypothesis will be examined that the prostaglandins modulate or mediate macula densa control of renin release. The relationship of the macula densa to the beta-adrenergic mechanism for renin release also will be examined. Assessment of macula densa function will be made in dogs pretreated with indomethacin to block endogenous prostaglandin synthesis. Renin secretion studies will be conducted in these indomethacin pretreated dogs during an intrarenal arterial infusion of hypertonic sodium chloride to increase the renal tubular load of sodium chloride presented to the macula densa receptor under the following experimental conditions: 1) prostacyclin stimulation, 2) isoproterenol stimulation, and 3) unstimulated basal conditions. Additional studies will evaluate the prostaglandin and macula densa mechanisms in the control of renin release and renal hemodynamic function in dogs with experimental high output heart failure. Also, experiments are planned to evaluate the hypothesis that calcium might function as a final common mediator in renin release. The role of calcium in renin release will be evaluated during intrarenal arterial infusions of calcium chloride in dogs pretreated with indomethacin under the following experimental conditions: 1) prostacyclin stimulation, 2) isoproterenol stimulation, 3) decreased renal perfusion pressure, and 4) unstimulated basal conditions.